Automated analyzers, commonly found in clinical laboratories, handle a plurality of samples and are known for identifying analytes in a patient fluid such as blood or sera. Sample fluids are placed into a form which is appropriate to the measurement technique. In typical wet chemistry systems, sample is generally placed in a sample vessel such as a cup or tube in the analyzer so that aliquots can be dispersed to reaction cuvettes or some other type of reaction vessel. A probe or proboscis using appropriate fluidics such as pumps, valves, and liquid transfer lines such as pipes and tubing and driven by pressure or vacuum are often used to meter and transfer a predetermined quantity of sample from the sample vessel to the reaction vessel. In the preparation of an assay, the sample probe or a different probe or proboscis is often required to deliver diluent to the reaction vessel, particularly when a relatively large amount of analyte is expected or found in the sample. A wash solution(s) is also generally needed to clean a nondisposable metering probe. In this instance and as in the preceding, fluidics are needed to accurately meter and deliver wash solutions and diluents.
In addition to sample preparation and delivery, the action taken on the sample that manifests a measurement often requires dispensing of a reagent, substrate, or other substance that combines with the sample to create some noticeable event such as fluorescence or absorbance of light. Several different substances are frequently combined with the sample to attain the detectable event. This is particularly true with immunoassays since they often require multiple reagents and wash steps. For example, in certain assays, a signal reagent is dispensed by a fluidic pump system from a reagent supply onto a bound antibody in a reaction well for detection by a luminometer.
Pumping/metering systems used on clinical analyzers, see FIG. 1, such as those manufactured by the Johnson and Johnson Company, among others, can include at least one variable speed pump which is used to both aspirate a quantity of fluid from a fluid supply, such as signal reagent, and then meter the aspirated fluid into a reaction vessel. Such variable speed pumps are useful in that some do not contain valves or seals and also are constructed from inert materials, which makes their application in the field of clinical chemistry a desired one. Moreover, the mechanical design of the pump affords savings in space and manufacturability, which is not found in other conventional servo or other constant speed pump types.
An exemplary variable speed pump used in the above pumping/metering system of a clinical analyzer utilizes mechanical means such as an eccentric cam, which is coupled to the pump piston. This form of interconnection in turn drives the piston both rotationally and reciprocally as shown in FIG. 4. A result of this operation is that the resulting fluid flow rate is variable throughout a metering cycle, this profile being consistent with the number of revolutions per minute of the motor driving the pump. For the pump shown in FIGS. 4(a)-4(d), the fluid flow rate profile for both the aspirate and the dispense phase of a fluid metering cycle is sinusoidal in nature ranging between zero at the onset and the conclusion of each phase and a maximum value there between as shown in FIG. 5.
As noted, there are certain advantages afforded by the above-noted pump designs. In the preceding pump design, for example, a single mechanism permits both rotational and translational movement of the piston. Therefore, utilization of these and other variable speed pump types is desirable for a number of varied types of metering systems covering numerous applications that involve liquid dispense. However, there are also some associated problems, depending on the end application, that can result with their implementation.
First and as previously noted, mechanical design of the above-described variable speed pump causes the fluid flow rate at the beginning of the dispense phase to rise gradually from zero and towards the end of the dispense phase to gradually drops to zero, as shown in the profile of FIG. 5. It has been determined that an insufficiently low velocity eliminates the fluid shear effect for fluid leaving a dispense tip or nozzle and therefore results in a substantial amount of fluid remaining either on the exterior of the probe, as a result of perfusion, if at the beginning of the dispense phase or within the metering probe, if at the end of the dispense phase. The amount of residual fluid can be variable which can be problematic. In particular, the metered volume variability is of particular concern when small volumes of fluid (e.g., less than 100 μl) are being metered, such as into a reaction vessel or well in the case of a clinical analyzer, and moreover when the fluid being metered is volatile. Residual fluid which is left on the end of the dispense tip can also evaporate various amounts when the duty cycle of the metering system is variable. For example and assuming this variation is as much as 2-3 μl, then evaporation of the residual fluid will result in about a 3 percent change at 100 μl of metered fluid volume and about a corresponding 30 percent change at 10 μl.
There are several other consequences/problems relating to the evaporation of residual fluid left at the tip of the metering probe, aside from errors in metered fluid volume. Residual fluid left on the end of the tip is exposed to atmosphere. Therefore and depending on the nature of the fluid, oxidation may result which could change the chemical nature of the fluid, thereby causing an impact upon the measurements taken, for example, by the clinical analyzer using the pump/metering system described herein, which can degrade performance. This latter impact can be more significant in nature than errors that are created in measured metered fluid volume.
In addition to the above consequences, dried residual fluid can also clog the orifice of the dispense nozzle and thus impact the flow of fluid therefrom. This issue is of particular concern when the orifice size is very small or when the flow direction and speed are critical parameters.
Yet another issue relating to residual fluid being left on the outside of the metering probe through perfusion is when the nozzle (e.g., metering probe) needs to be moved abruptly. The action of any abrupt movement can cause fluid to be dislodged from the exterior of the metering probe. Consequences from this undesired event range from cosmetic issues, given that periodic maintenance of the signal reagent module may be required, to a profound impact upon metering volume. The latter impact can be especially felt if the above described movement of the probe does not occur on each and every metering cycle.
Yet still another especially severe consequence, depending on the application, is cross contamination of fluids, which can have extremely disastrous results depending on the chemicals that are being metered.